Long noncoding RNAs: pivotal regulators in acute myeloid leukemia

Wei, Shuyong; Wang, Kankan

doi:10.1186/s40164-016-0059-9

Cited by 51 publications

(42 citation statements)

References 44 publications

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“…LncRNAs are primarily transcriptionally regulated by RNA polymerase II and serve a significant function in various process, including the splicing of introns, 5'-end capping and 3'-end polyadenylation (8), and have been demonstrated to affect histone modifications, binding of transcription factors to targeted genes and chromatin remodeling (9). LncRNAs have been indicated to affect cancer cell proliferation (10), metastasis (11), apoptosis (12) and autophagy (13) in a number of types of malignancy.…”

Section: Introductionmentioning

confidence: 99%

Long non‑coding RNA NNT‑AS1 contributes to cell proliferation, metastasis and apoptosis in human ovarian cancer

Huang

Shi

2018

Oncol Lett

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Ovarian cancer is a markedly heterogeneous malignancy characterized by various histological subtypes. Molecular biomarkers have been indicated to serve significant functions in the early diagnosis and treatment of early-stage ovarian cancer. However, the detailed mechanism underlying the tumorigenesis of ovarian cancer remains unclear. The present study aimed to identify a novel long non-coding RNA in patients with ovarian cancer. Nicotinamide nucleotide transhydrogenase-antisense 1 (NNT-AS1) was markedly downregulated in patients with ovarian cancer and in cultured human ovarian cancer cells. Knockdown of NNT-AS1 in the human ovarian cancer cell lines HO-8910 and SK-OV-3 promoted colony formation and arrested the cell cycle at G/G phase. Furthermore, Transwell demonstrated that the downregulation of NNT-AS1 increased cell migration and invasion by ~60 and 70%, respectively, in HO-8910 and SK-OV-3 cells. Furthermore, cell apoptosis was inhibited by the transfection of siNNT-AS1 in the two cell lines, whereas the relative activities of caspase-3 and caspase-9 were decreased. These results indicated a protective function of NNT-AS1 in human ovarian cancer, providing novel insights into the diagnosis and treatment of ovarian cancer in clinical settings.

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Section: Introductionmentioning

confidence: 99%

Long non‑coding RNA NNT‑AS1 contributes to cell proliferation, metastasis and apoptosis in human ovarian cancer

Huang

Shi

2018

Oncol Lett

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“…Moreover, lncRNAs are reported to be useful for disease prognosis, exemplified by the lncRNA HOTAIR (HOX transcript antisense RNA), which is upregulated in acute myeloid leukemia (AML) patients (23). So far, the majority of studies explored the role of single lncRNAs in leukemia including AML (24), chronic lymphocytic leukemia (CLL) (25) and pediatric ALL (26). Yet a comprehensive genomic and epigenetic delineation of lncRNAs deregulations in BCPALL subtypes, and their molecular and functional insights are lacking.…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNAs defining major subtypes of B cell precursor acute lymphoblastic leukemia

James

Schroêder

Neumann

et al. 2018

Preprint

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Recent studies implicated that long noncoding RNAs (lncRNAs) may play a role in the progression and development of acute lymphoblastic leukemia, however, this role is not yet clear. In order to unravel the role of lncRNAs associated with Bcell precursor Acute Lymphoblastic Leukemia (BCPALL) subtypes, we performed transcriptome sequencing and DNA methylation array across 82 BCPALL samples from three molecular subtypes (DUX4, Phlike, and Near Haploid or High Hyperdiploidy). Unsupervised clustering of BCPALL samples on the basis of their lncRNAs on transcriptome and DNA methylation profiles revealed robust clusters separating three molecular subtypes. Using extensive computational analysis, we developed a comprehensive catalog of 1235 aberrantly dysregulated BCPALL subtypespecific lncRNAs with altered expression and methylation patterns from three subtypes of BCPALL. By analyzing the coexpression of subtypespecific lncRNAs and proteincoding genes, we inferred key molecular processes in BCPALL subtypes. A strong correlation was identified between the DUX4 specific lncRNAs and activation of TGF and Hippo signaling pathways. Similarly, Phlike specific lncRNAs were β correlated with genes involved in activation of PI3KAKT, mTOR, and JAKSTAT signaling pathways. Interestingly, the relapsespecific differentially expressed lncRNAs correlated with the activation of metabolic and signaling pathways. Finally, we showed a set of epigenetically altered lncRNAs facilitating the expression of tumor genes located at their cis location. Overall, our study provides a comprehensive set of novel subtype and relapse specific lncRNAs in BCPALL. Our findings suggest a wide range of molecular pathways are associated with lncRNAs in BCPALL subtypes and provide a foundation for functional investigations that could lead to new therapeutic approaches. The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/365429 doi: bioRxiv preprint first posted online Jul. 9, 2018; Author SummaryAcute lymphoblastic leukemia is a heterogeneous blood cancer, with multiple molecular subtypes, and with high relapse rate. We are far from the complete understanding of the rationale behind these subtypes and high relapse rate. Long noncoding (lncRNAs) has emerged as a novel class of RNA due to its diverse mechanism in cancer development and progression. LncRNAs does not code for proteins and represent around 70% of human transcripts. Recently, there are a number of studies used lncRNAs expression profile in the classification of various cancers subtypes and displayed their correlation with genomic, epigenetic, pathological and clinical features in diverse cancers. Therefore, lncRNAs can account for heterogeneity and has independent prognostic value in various cancer subtypes.However, lncRNAs defining the molecular subtypes of BCPALL are not portrayed yet. Here, we describe a set of relapse and subtypespecific lncRNAs from three major BCPALL subtypes and define their potential functions and epigenetic regulation. Our data uncover ...

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“…Myeloid differentiation is usually considered to be dominantly controlled by highly myeloid-specific factors, however the widespread and abundant lncRNA Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) has been reported to be indispensable for normal myeloid differentiation [91]. Although not expressed in normal myelopoiesis, in an AML patient sample and an AML-derived HL-60 cell line, contain a rearrangement of the lncRNA gene Non-Structural Maintenance Of Chromosomes Element 2 Homolog (NSMCE2) that gives rise to two novel chimeric genes, PVT1-NSMCE2 and CCDC26-NSMCE2 [92].…”

Section: Long Non-coding Rna (Lncrnas)mentioning

confidence: 99%

Beyond mRNA: The role of non-coding RNAs in normal and aberrant hematopoiesis

Wilkes

Repellin

Sakamoto

2017

Molecular Genetics and Metabolism

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The role of non-coding Ribonucleic Acids (ncRNAs) in biology is currently an area of intense focus. Hematopoiesis requires rapidly changing regulatory molecules to guide appropriate differentiation and ncRNA are well suited for this. It is not surprising that virtually all aspects of hematopoiesis have roles for ncRNAs assigned to them and doubtlessly much more await characterization. Stem cell maintenance, lymphoid, myeloid and erythroid differentiation are all regulated by various ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and various transposable elements within the genome. As our understanding of the many and complex ncRNA roles continues to grow, new discoveries are challenging the existing classification schemes. In this review we briefly overview the broad categories of ncRNAs and discuss a few examples regulating normal and aberrant hematopoiesis.

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Long noncoding RNAs: pivotal regulators in acute myeloid leukemia

Cited by 51 publications

References 44 publications

Long non‑coding RNA NNT‑AS1 contributes to cell proliferation, metastasis and apoptosis in human ovarian cancer

Long non‑coding RNA NNT‑AS1 contributes to cell proliferation, metastasis and apoptosis in human ovarian cancer

Long non-coding RNAs defining major subtypes of B cell precursor acute lymphoblastic leukemia

Beyond mRNA: The role of non-coding RNAs in normal and aberrant hematopoiesis

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